Vital infections can present significant health threats, causing serious illnesses and, in some instances, death. For example, Acquired Immune Deficiency Syndrome (AIDS) has become a significant public health threat in recent years. The virus believed to be the causative agent of AIDS has been described by several names. It has been known as lymphadenopathy-associated virus (LAV), AIDS-related virus (ARV) and human immunodeficiency virus (HIV). Within the last few years, scientists have discovered that there are at least two distinct viruses, HIV-1 and HIV-2. HIV-1 is the virus originally isolated in 1983 (Ann. Virol. Inst. Pasteur, 135E:119-134 [1986]); HIV-2 was isolated by researchers in 1986 (see Nature, 326:662 [1987]). As used herein, HIV refers to these viruses generically.
A number of synthetic compounds have been found to possess anti-HIV activity. Most, if not all, of these compounds are nucleotide analogs, such as azidothymidine (AZT) and dideoxyiosine (ddI). See, for example, Science 243: 1731 ( 1989 ); Ann. Intern. Med. 122:812 ( 1990 ); Antimicrob. Agents Chemother. 34:1061 (1990); and N. E. J. Med. 322:133 and 1340 (1990). Although these compounds are useful, additional compounds are sought.
Other viruses also present significant health risks. Influenza is an acute febrile viral illness that yearly spreads to epidemic proportions, and periodically occurs in worldwide or pandemic form. Human influenza viruses are divided on the basis of the distinctive antigenic characteristics into three major types, A, B, and C, which have shared no cross-reacting antigens.
Influenza virus is transmitted from person to person as an airborne infection. The virus may localize in the respiratory, nasal and/or bronchial tracts. Symptoms of the influenza virus can range from severe retro-orbital headache, nonbacterial pharyngitis and laryngitis to tracheobronchitis or primary viral pneumonia. Influenza infections also can be associated with several nonspecific phenomena that impair antibacterial resistance factors, such as bacterial pneumonia.
Anti-influenza agents include amantadine hydrochloride. Additionally, vaccination and previous infection actively immunize against reinfection by influenza viruses with homologous or closely related surface antigens. The vaccination can be a live or killed influenza virus. Although vaccines have proven to be useful, there are still problems with vaccine production, such as the annual decision as to which antigen should be incorporated into the vaccine and how many antigens should be included.
Herpes is vital disease with no current cure. Two major antigenic forms of the herpes simples virus have been identified: herpes simplex type 1 virus (HSV-1) (oral) and herpes simplex type 2 virus (HSV-2) (genital). The genital infection due to HSV-2 is one of the most common venereal disease in the United States, reaching epidemic portions over the last decade.
A striking feature of all members of the herpes virus family is their ability to persist in a clinically quiescent or latent state. Features of HSV-1 are fever blisters, keratitis, and rarely, encephalitis. Features of HSV-2 are genital infections, such as urethritis in males and vulvitis, vaginitis, and cervicitis in females. Furthermore, a pregnant woman with an active infection at the time of delivery can transmit the virus to her newborn child.
Over the years, various substances have been postulated as medications for the various kinds of herpes. Examples include a mixture of vitamin C and vitamin P (U.S. Pat. No. 4,049,798), a mixture of kelp and a carrier (U.S. Pat. No. 4,117,120), extract of mountain ash berries (U.S. Pat. No. 4,132,782), a water soluble extract from marine red alga (U.S. Pat. No. 4,162,782), antiviral lignosulfate (U.S. Pat. No. 4,185,097), 1-amino-2,4- ethanobicyclo[3,3,1]nonane or salts thereof (U.S. Pat. No. 4,230,725), and a suspension of boric acid, tannic acid, and salicylic acid, preferably in an ethanol solvent/carrier (U.S. Pat. No. 4,285,934). Additionally, Acyclovir is an antiviral agent that has demonstrated positive therapeutic effect in the treatment of genital herpes virus infection.
Although agents are known which show at least a degree of effectiveness in inhibiting replication of these and other viruses, additional agents are sought.
Accordingly, it is an object of this invention to provide novel synthetic compounds having potent anti-viral activity. It is a further object of this invention to provide novel synthetic compounds having anti-vital activity that are not nucleotide analogs. Other objectives of this invention will become apparent from the following description and accompanying claims.